Abstract A129: Alpha-fetoprotein-derived peptide (AFPep): A novel drug in translational studies for the treatment and prevention of breast cancer.

A129

It has been well established that parity is associated with reduced lifetime risk for breast cancer. Recent U.S. Census data note that the proportion of American women who remain nulliparous has doubled over the last 30 years. These data suggest that the incidence of breast cancer will increase in the coming years. Is there a molecule in pregnancy that can be isolated, shown to inhibit breast cancer, and be converted into a drug that can be used to treat and prevent breast cancer?

The studies reported here demonstrate that a-fetoprotein (AFP) is such a molecule, that the anti-breast cancer site within that molecule is an 8-amino acid sequence in the third domain of the protein, and that this site has been synthesized in a form that can be used as a novel, non-toxic drug for the treatment and chemoprevention of breast cancer. We refer to this agent as AFPep.

AFPep is active after oral administration. It stops the growth of human breast cancers growing as xenografts in immune deficient mice, and it prevents the development of carcinogen-induced mammary cancers in rats. Its anti-breast cancer activity is additive in combination with tamoxifen, and it prevents the uterine hyperplasia induced by tamoxifen. Moreover, AFPep is active against breast cancers which have become resistant to tamoxifen. Its anti-oncotic mechanism is different from that of tamoxifen, aromatase inhibitors, anti-gonadotropins, and cytotoxic chemotherapy. There has been no evidence of toxicity in mice and rats receiving AFPep even when its dose was escalated 100-fold above its effective dose. Grant proposals are currently in review to support further development of AFPep including completion of its preclinical toxicology and initiation of Phase I clinical trials.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):A129.